D-Glucose upregulates adenosine transport in cultured human aortic smooth muscle cells

George P.H. Leung, Ricky Y.K. Man, Chung Ming Tse

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The etiology of the atherosclerosis that occurs in diabetes mellitus is unclear. Adenosine has been shown to inhibit growth of rat aortic smooth muscle cells. Nucleoside transporters play an integral role in adenosine function by regulating adenosine levels in the vicinity of adenosine receptors. Therefore, we studied the effect of 25 mM D-glucose, which mimics hyperglycemia of diabetes, on adenosine transport in cultured human aortic smooth muscle cells (HASMCs). Although RT-PCR demonstrated the presence of equilibrative nucleoside transporter-1 (ENT-1) and ENT-2 mRNA, functional studies revealed that adenosine transport in HASMCs was predominantly mediated by ENT-1 and inhibited by nitrobenzylmercaptopurine riboside (NBMPR, IC50 = 0.69 ± 0.05 nM). Adenosine transport in HASMCs was increased by >30% after treatment for 48 h with 25 mM D-glucose, but not with equimolar D-mannitol and L-glucose. Kinetic studies showed that D-glucose increased Vmax of adenosine transport without affecting Km. Similarly, D-glucose increased B max of high-affinity [3H]NBMPR binding, while the dissociation constant (Kd) was not changed. Consistent with these observations, 25 mM D-glucose increased mRNA and protein expression of ENT-1. Treatment of serum-starved cells with the selective inhibitors of MAPK/ERK, PD-98059 (40 μM) and U-0126 (10 μM), abolished the effect of D-glucose on ENT-1. We conclude that D-glucose upregulates the protein and message expression and functional activity of ENT-1 in HASMCs, possibly via MAPK/ ERK-dependent pathways. Pathologically, the increase in ENT-1 activity in diabetes may affect the availability of adenosine in the vicinity of adenosine receptors and, thus, alter vascular functions in diabetes.

Original languageEnglish (US)
Pages (from-to)H2756-H2762
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 57-6
StatePublished - Jun 2005


  • Diabetes
  • Nucleoside transporter

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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